Lin Karen, Hasegawa Karin, Rapelli Vindhya, Yang Jie, Parsey Ramin, DeLorenzo Christine
Cornell University.
Stony Brook University.
Res Sq. 2025 May 8:rs.3.rs-6257703. doi: 10.21203/rs.3.rs-6257703/v1.
The link between obesity and depression is bidirectional and antidepressant efficacy is reduced in obese individuals. To probe this mechanism, anthropometric measures (body mass index [BMI] and waist circumference [WC]) from 85 participants (n = 56 females, n = 29 males) with Major Depressive Disorder (MDD) were acquired. Participants then received simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) before and after treatment with a double-blind randomized trial of escitalopram. Linear mixed models were used to examine the association of continuous and categorical anthropometric measures with pretreatment amygdala and hippocampus volumes and metabolism, controlling for covariates. Similar models assessed the association with percent change in brain volume and metabolism with treatment, controlling for treatment type. Pretreatment, obesity was significantly positively associated with amygdala (p = 0.0160 and 0.0154, for WC and BMI, respectively) and hippocampus (p = 0.0221 for BMI) volume, but not metabolism. With treatment, each additional inch of WC (or each lb/in of BMI) was associated with a -0.38% (or -0.26%) treatment-induced change in amygdala volume. In fact, past 37.29 in (border of increased risk for males, substantially increased risk for females) or 30.63 lb/in (obese range), the percent change in amygdala volume with treatment shifts from positive (increasing) to negative (decreasing). Further, for every 1 lb/in in BMI, there was a 1.03% (amygdala) or 0.99% (hippocampus) increase in metabolism with treatment. This multimodal study is the first to suggests that obesity-related factors may alter the structure and metabolism of the amygdala and hippocampus, potentially reducing antidepressant effectiveness in MDD.
肥胖与抑郁症之间的联系是双向的，肥胖个体的抗抑郁药疗效会降低。为探究这一机制，我们收集了85名患有重度抑郁症（MDD）的参与者（n = 56名女性，n = 29名男性）的人体测量指标（体重指数[BMI]和腰围[WC]）。参与者随后接受了艾司西酞普兰双盲随机试验治疗前后的同步正电子发射断层扫描（PET）/磁共振成像（MRI）。使用线性混合模型来检验连续和分类人体测量指标与治疗前杏仁核和海马体体积及代谢之间的关联，并控制协变量。类似模型评估了与治疗后脑体积和代谢变化百分比的关联，并控制治疗类型。治疗前，肥胖与杏仁核（WC和BMI分别为p = 0.0160和0.0154）和海马体（BMI为p = 0.0221）体积显著正相关，但与代谢无关。治疗后，WC每增加一英寸（或BMI每增加一磅/英寸），杏仁核体积的治疗诱导变化为 -0.38%（或 -0.26%）。事实上，超过37.29英寸（男性风险增加的边界，女性风险大幅增加）或30.63磅/英寸（肥胖范围）后，治疗后杏仁核体积的变化百分比从正向（增加）转变为负向（减少）。此外，BMI每增加一磅/英寸，治疗后代谢增加1.03%（杏仁核）或0.99%（海马体）。这项多模态研究首次表明，肥胖相关因素可能会改变杏仁核和海马体的结构与代谢，从而可能降低MDD患者的抗抑郁效果。
